TIMP1 (Tissue Inhibitor of Metalloproteinases-1) is a multifunctional protein that primarily inhibits matrix metalloproteinases (MMPs) by forming one-to-one complexes with target enzymes, but also exhibits significant non-canonical signaling activities. TIMP1 functions as a metalloproteinase inhibitor that binds to the catalytic zinc cofactor of MMPs, irreversibly inactivating enzymes including MMP1, MMP2, MMP3, and others 1. Beyond its inhibitory role, TIMP1 acts as a signaling molecule through interactions with cell surface receptors CD63 and β1-integrin, forming a membrane complex that activates cellular pathways involved in proliferation, migration, and survival 1. In cancer contexts, TIMP1 demonstrates complex dual roles. It can promote tumor progression through several mechanisms: triggering neutrophil extracellular trap formation via CD63/ERK signaling in pancreatic cancer 2, stimulating Schwann cell proliferation and perineural invasion through CD63/PI3K/AKT signaling 3, and reprogramming senescence-associated secretory phenotypes when deficient, promoting prostate cancer metastasis 4. Clinically, elevated TIMP1 expression correlates with poor prognosis in multiple cancers including gastric cancer 5. TIMP1 also plays roles in wound healing and tissue repair, being upregulated during reepithelialization 6, and shows protective effects against photoaging when delivered via mesenchymal stem cell-derived extracellular vesicles 7.